Anti-obesity Effects of Panax ginseng-derived exosomes via AMPK-mediated inhibition of adipocyte differentiation and lipogenesis

This study investigated the anti-obesity potential of Panax ginseng-derived exosomes (PGE) by evaluating their influence on energy metabolism, adipogenesis, and lipid accumulation. PGEs were isolated using a tangential flow filtration system, yielding particles with an average diameter of 159.5 nm and a concentration of 3.9 × 10¹² particles/mL. In 3T3-L1 preadipocytes, PGE treatment resulted in a 72.1% reduction in lipid accumulation, as demonstrated by Oil Red O staining, indicating significant inhibition of adipogenic differentiation. Elevated expression of surface markers TET-8 (147.2%) verified the exosomal nature of the isolated vesicles. To determine their role in adipocyte differentiation, we analyzed gene and protein expression of key adipogenic markers-peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer-binding protein alpha and beta, and fatty acid-binding protein 4-revealing reductions of 23.6-35.6% and 26.7-35.2%, respectively. These results indicate downregulation of transcriptional and translational pathways driving adipogenesis. Lipogenic regulators, including sterol regulatory element-binding protein 1c, acetyl-CoA carboxylase, and fatty acid synthase, were also suppressed by 24.9-41.0% (gene) and 22.8-24.5% (protein), indicating impaired fatty acid synthesis. Conversely, AMP-activated protein kinase (AMPK) expression increased by up to 53.8% (gene) and 47.9% (protein), implying activation of energy homeostasis signaling. Immunofluorescence analysis showed a reduction in the MitoTracker/DAPI ratio (57.7-60.0%) and an increase in the F-actin/DAPI ratio (39.5-60.8%), indicating decreased mitochondrial activity and enhanced cytoskeletal integrity. These molecular changes were accompanied by AMPK activation and PPAR-γ inhibition. Collectively, these findings underscore the potential of PGEs as bioactive agents for obesity management by concurrently inhibiting adipogenesis and lipogenesis, providing a strong basis for their application in anti-obesity functional foods and pharmaceutical products.